Aminosterol compounds useful as inhibitors of the sodium/proton exchanger (NHE), pharmaceutical methods and compositions employing such inhibitors, and processes for evaluating the NHE-inhibitory efficacy of compounds

Abstract

Aminosterol compounds are described that are useful as inhibitors of the sodium/proton exchanger (NHE). Methods of using such aminosterols compounds are also enclosed, including those employing compounds that are inhibitors of a spectrum of NHEs as well as those using compounds that are inhibitors of only one specific NHE. Advantageous screening techniques and assays for evaluating a compound's therapeutic activity are also disclosed.

1 - 3 . (canceled)  
   
   
       4 . A method of inhibiting neovascularization in a mammalian eye, comprising administering to the mammal in need thereof a composition comprising an amount of squalamine or a pharmaceutically acceptable salt thereof effective to inhibit the neovascularization.  
   
   
       5 . The method of  claim 4 , wherein the effective amount is about 0.1 to about 10 mg/kg body weight.  
   
   
       6 . The method of  claim 4 , wherein the neovascularization is associated with macular degeneration.  
   
   
       7 . The method of  claim 6 , wherein the composition is administered intravenously or subcutaneously.  
   
   
       8 . The method of  claim 6 , wherein the composition is administered topically.  
   
   
       9 . The method of  claim 4 , wherein the composition is used in combination with at least one other therapy for inhibiting neovascularization in a mammalian eye.  
   
   
       10 . The method of  claim 6 , wherein the composition is used in combination with at least one other therapy for treating macular degeneration in a mammal.  
   
   
       11 . A method of treating macular degeneration in a mammal, comprising administering to the mammal a composition comprising an amount of squalamine or a pharmaceutically acceptable salt thereof effective to treat the macular degeneration.  
   
   
       12 . The method of  claim 11 , wherein the effective amount is about 0.1 to about 10 mg/kg body weight.  
   
   
       13 . The method of  claim 11 , wherein the macular degeneration is age-related macular degeneration.  
   
   
       14 . The method of  claim 13 , wherein the age-related macular degeneration is the wet form.  
   
   
       15 . The method of  claim 13 , wherein the age-related macular degeneration is the dry form.  
   
   
       16 . The method of  claim 4  or  claim 11 , wherein the mammal is a human.  
   
   
       17 . The method of  claim 11 , wherein the composition is administered intravenously.  
   
   
       18 . A method of treating macular degeneration in a human, comprising administering systemically to the human in need of treatment, a composition comprising an amount of squalamine or a pharmaceutically acceptable salt thereof effective to treat the macular degeneration.  
   
   
       19 . The method of  claim 18 , wherein the systemic administration is selected from the group consisting of intravenous, subcutaneous and intramuscular injection.  
   
   
       20 . The method of  claim 18 , wherein the method consists essentially of administering to the human in need of treatment, a composition comprising an amount of squalamine or a pharmaceutically acceptable salt thereof effective to treat the macular degeneration.  
   
   
       21 . The method of  claim 18 , wherein the method consists of administering to the human in need of treatment, a composition comprising an amount of squalamine or a pharmaceutically acceptable salt thereof effective to treat the macular degeneration.  
   
   
       22 . The method of any one of claims  4 ,  11  or  18  wherein the composition consists essentially of squalamine.  
   
   
       23 . The method of any one of claims  4 ,  11  or  18  wherein the composition consists of squalamine.  
   
   
       24 . The method of any one of claims  4 ,  11  or  18  wherein the composition further comprises one or more pharmaceutically acceptable excipients.